Hypersensitivity Flashcards
What is hypersensitivity?
Exaggerated or abnormal immune response to an antigen resulting in inflammation and tissue damage
Which Type of hypersensitivity is most common?
Type 1
What is the immune reactant of Type I hypersensitivity?
IgE
What are common syndromes associated with Type1?
Systemic Anaphylaxis Acute Urticaria (wheel-and-flare) Allergic rhinitis asthma food allergy
What is the antigen for Type1 disorders?
Soluble antigen
The most serious Type 1 disorder is _________ and the route of entry for the antigen is ______ or _____.
Systemic Anaphylaxis
intravenous
oral
Edema, increased vascular permeability, tracheal occlusion are all responses due to ______.
Systemic anaphylaxis
With Wheel-and-flare disorders the antigen is acquired through ______; whereas antigens associated with hay fever and asthma are acquired through______.
the skin
inhalation
Type 1 hypersensitivity is referred to as immediate because it occurs within minutes after ________ to antigen/allergen.
REexposure
Which type of hypersensitivity is associated with “mast cell mediated vascular and smooth muscle reaction and inflammation?”
Type 1
Which type of hypersensitivity is associated with “mast cell mediated vascular and smooth muscle reaction and inflammation?”
Type 1
What is sensitization?
Initial exposure to antigen and production of IgE antibodies
IgE antibodies are bound by ___ receptors on _____ cells.
Fc receptors
Mast cells
What are the two stages of the biphasic response in Type 1 Hypersensitivity?
- Immediate Effects (dilation of vessels, inc permeability)
2. Late Response (inflammation)
What are the two stages of the biphasic response in Type 1 Hypersensitivity?
- Immediate Effects (dilation of vessels, inc permeability)
2. Late Response (inflammation)
Initial exposure to antigen results in the activation of Th2 cells and the release of ____ cytokines. These cytokines will then trigger the production of IgE associated with Type 1 hypersensitivity.
IL-4, IL-5, and IL-13
In Type 1 hypersensitivity, a secondary exposure to a particular antigen will result in activation of _______ cells.
Mast
Mast cell degranulation results in the increase of vasoactive amines, such as ______ and ______, as well as proteases.
Histamine
Serotonin
What are two important lipid mediators that are synthesized and secreted by mast cells?
Prostaglandins (vasoconstriction of lungs)
Leukotrienes (bronchocontriction, inc. vascular permiab.)
Prostaglandins and leukotrienes are derived from ______ acid.
Arachidonic
Leukotrienes are referred to as slow-reacting substance of anaphylaxis (SRS-A) and act to _______ vascular permeability and constrict the bronchi.
increase
What does IL-5 recruit?
Eosinophils
In the late phase response of Type1 Hypersensitivity, there is a synthesis and secretion of important _____.
Cytokines and Chemokines
*IL-4, IL-5, TNF-alpha
Eosinophils release granules that contain _____ that will damage indiscriminately.
ROS
Eosinophils release granules that contain _____ that will damage indiscriminately.
ROS
Initiation of mast cell degranulation involves ______.
ITAMs
What are the cellular events of mast cell activation?
- Bind ______
- Trigger _______
- Activate _______ and _______
- ______ will lead to expression of cytokines
- ______ will lead to the release of granules
- allergen at cell surface
- ITAMs
- PKC, MAP Kinase
- MAP Kinase
- PKC
What are two functions of MAP kinase in mast cell activation?
- “Cytokine expression”
2. Initiate PLA2 that will create arachidonic acid and eventually “Lipid Mediators”
During mast cell activation, ______ is involved in the creation of lipid mediators and cytokines; whereas, ______ is involved in the release of granules.
MAP Kinase
PKC
Asthmatics tend to produce _____ and form thicker _____ that restrict the airway.
Extra mucous
tracheal walls
______ are a common trigger of asthma.
Dust mites
What enzyme do dust mites produce that cleaves tight junctions and allows mites to enter/trigger mast cell degranulation?
Der p 1 (derp)
Two common long-term control medications for asthma are 1._______ and 2._______.
- Inhaled Corticosteroids
2. Leukotriene Modifiers
The _____ and ____ __ _____ of allergens will determine the type of IgE-mediated allergic reaction that results.
Dose
Route of entry
The “wheel-and-flare” reaction in the skin is in response to ______ cell mediators and local blood vessel dilation.
mast
Inflammation results from mast cell release of _______ and _______.
Cytokines
Lipid Mediators
Bronchoconstriction, intestinal hypermotility, and vasular leakage result from mast cell release of _____ and ________.
Biogenic amines
Lipid Mediators
What are the three important steps in Type 1 Hypersensitivity?
- Mast Cell degranulation
- Synthesis and secretion of lipid mediators
- Cytokine release
What are the three important steps in Type 1 Hypersensitivity?
- Mast Cell degranulation
- Synthesis and secretion of lipid mediators
- Cytokine release
Type II Hypersensitivity involves _____ antibody binding to antigens on self cell surfaces.
IgG
Type I involves soluble antigen; whereas, Type II involves _____ antigen or ______ receptor.
cell-associated antigen
cell-surface receptor
Autoimmune hemolytic anemia, myasthenia gravis, and Graves disease are associated with Type _______.
Type II Hypersensitivity
Type II can activate _______ and result in membrane attack complex formation that leads to destruction of cells, inflammation, or interference with normal cell function.
Complement
Hemolytic disease of newborns is a Type ___ disorder in which maternal ____ target fetal ______ for destruction.
II
Antibodies
RBCs
______ Disease is a type II hypersensitivity associated with overproduction of thyroid hormone.
Graves
What is the Type II disease associated with muscle weakness from blockage of the Ach receptor?
Myasthenia Gravis
Autoimmune hemolytic anemia is commonly treated with _____ (i.e. Prednisone) or _______.
Corticosteroids
Blood Transfusion
In Type II hypersensitivity, host _____ binds to foreign ____ on cell surfaces or binds to ____.
antibody
antigen
self-antigen
In Type II hypersensitivity, host _____ binds to foreign ____ on cell surfaces or binds to ____.
antibody
antigen
self-antigen
Which type of hypersensitivity is associated with Ag-Ab complexes that clump and deposit in blood vessels or tissues and then attract acute inflammatory reaction?
Type III
immune complex mediated
______ aggregates fix complement and are cleared from circulation, but ____ complexes formed in Ag excess will deposit in vessels or tissue.
Large = cleared Small = deposit
Small deposited complexes will ligate _____ receptors on leukocytes and lead to tissue damage.
Fc
Immune deposits in Type III HS will generally accumulate at sites where antigen is localized or at sites of ______ or high ______.
Turbulence (blood flow)
Pressure (kidneys)
Immune complexes associated with Type III HS will trigger inflammation via what three mechanisms?
- Mast cell activation
- Macrophage release of TNF-alpha and IL-1 (create Reactive Epithelium)
- Complement activation (release more histamine and serotonin)
Which cytokines will induce a “reactive epithelium” and from which cell are they released?
TNF-alpha, IL-1
Released from MACROPHAGEs
The complement cascade in Type III HS will stimulate mast cells to release more ______, _______, and chemotactic factors.
histamine
serotonin
Cells bearing Fc receptors for _____ are crucial for antibody-complex-mediated hypersensitivity.
IgG
Cells bearing Fc receptors for _____ are crucial for antibody-complex-mediated hypersensitivity.
IgG
What is the arthus reaction?
a type III HS reaction in the skin that is triggered by IgG
What is the arthus reaction?
a type III HS reaction in the skin that is triggered by IgG
Which complement molecule will activate leukocytes?
C5a
Which cytokines induce the formation of reactive epithelium?
TNF-alpha
IL-1
_____ reaction typically occurs in vessel walls, pleura, pericardium, synovium, or glomeruli and can result from repeated subcutaneous injections.
Arthus
Serum sickness is a classic example of transient ________ immune complex-mediated syndrome that will usually resolve itself with Ab response.
Systemic
Which (life-threatening) Type III HS disorder involves IgG antibody directed against DNA in skin, joints, and kidneys?
SLE
Arthus reaction, Serum Sickness, and SLE are examples of ________ Hypersensitivity. This Type is also known as?
Type III
Immune-Complex Mediated
Arthus reaction, Serum Sickness, and SLE are examples of ________ Hypersensitivity. This Type is also known as?
Type III
Immune-Complex Mediated
Which type of hypersensitivity involves T cells?
Type IV
In Type IV HS, ______ infiltration is induced by Ag specific ____ cells in a SENSITIZED individual.
Macrophage
T
What is DTH?
Delayed Type Hypersensitivity
Type IV HS
Contact dermatitis is an example of _____ hypersensitivity.
Type IV
Macrophages, _______ T Cells, and NK cells are important effector cells in the DTH response.
CD8+
DTH = Type IV
What are haptens?
Small molecules that must become bound to a larger carrier molecule in order to illicit an immune or inflammatory response (Generally responsible for initiating Type IV hypersensitivity)
Type IV hypersensitivity: Antigen presented by APCs will activate _____ cells that will then secrete _____ and activate macrophages.
T helper
Cytokines
The tuberculin test for TB involves a _______ inflammatory reaction that is mediated by _____ cells.
T cell-mediated
Th1
The tuberculin test for TB involves a _______ inflammatory reaction that is mediated by _____ cells.
T cell-mediated
Th1
Haptens (highly reactive small molecules) are complexed with skin proteins and are internalized by APCs which will lead to inflammation associated with ______ (ex. poison ivy).
Contact Dermatitis
Contact dermatitis can be elicited by either ____ or ____.
CD4 T Cells
CD8 T Cells
What are the two phases of contact hypersensitivity?
- sensitization
2. Elicitation
When does sensitization occur? How long does it take? What type of T cells are formed as a result?
During first exposure to antigen
Takes 10-14 days
CD4+ Memory T Cells
When does elicitation occur? How long does it take? What will keratinocytes in the activated membrane release?
upon RE-EXPOSURE to a particular antigen
24-48 hours after presentation to memory cells
TNF-alpha and proinflammatory cytokines (IL-1)
True or False: Contact Dermatitis is a Type III Hypersensitivity disorder that can be caused by allergens such as latex, solvents, medications, and fabrics.
False: contact dermatitis IS associated with these allergens but CD is a Type IV hypersensitivity disorder
True or False: Contact Dermatitis is a Type III Hypersensitivity disorder that can be caused by allergens such as latex, solvents, medications, and fabrics.
False: contact dermatitis IS associated with these allergens but CD is a Type IV hypersensitivity disorder
Mast cell degranulation that is associated with Chronic Asthma will lead to _____ and ______ influx.
Th2
Eosinophil
Which cytokine is closely associated with eosinophils?
IL-5
Inflammatory Bowel Disease (Crohn’s) is thought to be due to unresolved ______.
Delayed Type Hypersensitivity (DTH): Type IV
Types ____ and _____ involve IgG.
II
III
Type _____ involves IgE.
I
Soluble antigen is associated with Types ____, _____, and _____.
I
III
IV
(not II)
Match the Effector with the Type of HS:
- Complement
- Macrophage activation, Eosinophils
- Mast Cells
- Complement FcR cells, Antibody
- Type III
- Type IV
- Type I
- Type II
Vasculitis, Nephritis, and Arthritis are associated with which hypersensitivity type?
Type III
In Type IV Hypersensitivity, Th1 cells will activate ______; whereas, Th2 cells will activate ________.
Macrophages
Eosinophils
What is the mneumonic for remembering the different hypersensitivity types?
ACID
Type 1: Allergic (anaphylaxis)
Type 2: Cytotoxic (drug allergies,
Type 3: Immune Complex (deposits in tissue/vessels)
Type 4: Delayed (contact dermatitis, TB testing)